The present invention relates to novel antimicrobial disclosing agents for use in the improvement of oral hygiene practice.
Dental plaque is a well-organized structure which forms on tooth surfaces and restorations. It consists mainly of bacteria surrounded by a matrix derived primarily from saliva and the bacteria themselves. Plaque differs from other soft tooth deposits such as material alba and food debris in that it has a definite architecture and cannot be flushed away by rinsing with water.
It is well established that dental plaque plays a major role in the etiology of periodontal disease and caries. Although the exact manner in which plaque contributes to these disease states is not known at present, it is appreciated that effective and thorough removal of these deposits is absolutely essential for control, and that a removal program must be established as part of the treatment plan for every dental patient. For this program to be effective, the patient must be motivated to carry out thorough daily plaque control techniques. Motivation can be achieved, however, only by establishing goals that are meaningful and attainable by the patient. Experience has shown that most patients would not be sufficiently motivated to practice good oral hygiene if they were simply told that plaque is a bacterial colony growing on their teeth, and that plaque produces gingival disease and caries and must be removed daily. However, the entire concept of what plaque is and what it does to tissue can be made vital and important to the patient by visualization, whereby every patient is shown his plaque in situ and under the phase contrast of a microscope. The patient may also observe the diseased gingival are as and their juxtaposition to the places of plaque accumulations. These visual demonstrations serve two main purposes. First, it shows the patient that he does indeed have these dangerous bacterial deposits called plaque on his teeth. Secondly, in the microscopic visualization, he sees that those innocent looking masses are composed of millions of living bacteria of differing shapes. Experience has shown that the technique of visualization of plaque generates in patients a true interest in plaque and an obvious and apparent concern for its prompt removal.
Recent evidence has shown that plaque has a great destructive potential and, under varying conditions, can cause gingivitis and periodontitis, produce dental caries, or form into calculus. It has also been established that plaque accumulation which is allowed to develop without removal in many cases may cause gingivitis within one to twenty one days. There is also recent evidence indicating that plaque with all of its components may be capable of producing an allergic response in adjacent soft tissues.
This rather substantial potential destructiveness has given rise to the increased attention and the resultant recent attempts to educate the public in the control of plaque. Generally, this control has adopted an approach of oral lavage and focused on the tasks such as brushing, stimulating, massaging, rinsing, spraying, and the like. However, while these techniques are effective for the removal of food debris and similar foreign matter, they are not very effective for removal of plaque. Plaque formation is transparent and is therefor not readily visible, particularly to one who is not skilled in its detection, and most often its removal occurs mainly by accident during oral lavage.
In order to increase the effectiveness of plaque detection and removal, there has been a recent introduction into the marketplace of staining compositions or so-called disclosing compositions. These disclosing compositions contain coloring agents or dyes which are designed to be absorbed by the plaque to make the plaque visually distinguishable form the remainder of the oral cavity. The active staining ingredient in most of these commercially available disclosing compositions is generally iodine or several organic dyes which serve as the primary diagnostic agent.
Organic dyes have been almost universally adopted for use in the commercially available disclosing compositions because of their higher degree of effectiveness. However, in almost all of these cases these dyes have a highly unpalatable and objectionable taste which is not effectively masked by any known flavoring agent or sweetner.
In order to obviate the need of disclosing solutions as a diagnostic device, there has been a recent introduction in the marketplace of fluoresecent light detection systems. These types of light detection systems rely upon compositions which are introduceable into the oral cavity and contain an ingredient which is fluorescent when activated by a proper light source. It is contended that the fluorescent ingredient or dye is absorbable by the plaque and that the fluorescent dye will only flouresce on the areas containing plaque formation when excited by the proper light source. However, in most cases the dye fluorseces at the same color as the enamel, and, therefore, the plaque is not readily distinguishable. Furthermore, the purchase cost for these systems generally have militated against their widespread use.
It has been found that benzo-c-phenanthridine alkaloids, which have antimicrobial properties, are also effective in disclosing plaque under long UV light. These compounds are of particular use in disclosing plaque because they also have a positive effect on the oral cavity and they are substantive to mouth tissue.
One of the important sources of the benzo-c-phenanthridine alkaloids is a perennial herb native to North Americla called Sanguinaria candensis Linne (Family: Papvaracea), commonly known as blood root, redroot, puccoon, and the like. The plant contains benzo-c-phenanthridine alkaloids including sanguinarine, chelerythrine, and several others. The maining benzo-c-phenanthridine alkaloids useful as antimicrobial agents are sanguinarine, sanguirubine, sanguilutine, chelerythrine, homochelidonene, chelirubine, protopine, and mixtures thereof.
The pure chemicals sanguinarine, cherlerytherine, and other benzo-c-phenanthridine alkaloids can be isolated form other plants besides Sanguinaria. Also, they are available, although rarely, form some chemical supply houses. Semi-purified forms of the alkaloids are commercially available, and these are generally referred to as sanguinarine nitrate and sanguinarine sulfate. These "salts" are the salts of the mixed alkaloids of the plant Sanguinaria: mainly sanguinarine, chelerythrine, and protopine. While few references can be found in the literature regarding the usage of any of the pure benzo-c-phenanthridine alkaloids, plants containing such compounds have been used for medical purposes for quite some time for a wide variety of ailments.
An early U.S. Pat. No. 209,331, discloses the use of bloodroot, zinc chloride, and kerosene oil in equal proportions for treating open sores. U.S. Pat. No. 433,257 describes a salve of pulverized bloodroot, armenian bole, powdered rosin, lard, and Stockholm tar for use in the treatment of piles. U.S. Pat. No. 2,344,830, discloses the use of a mixture of zinc chloride, stibnite, and bloodroot, to fix and outline diseased tissue for excision by surgery.
Several more recent patents have disclosed the use of extracts of Sanguinaria for treating the oral cavity for conditioning oral tissue as well as in preventing and treating gingivitis, periodontitis, and mouth odors. Some of the patents describing the use of sanguinaria extracts as antimicrobial agents are U.S. Pat. No. 4,145,412; U.S. Pat. No. 4,406,881; U.K. Pat. No. 2,042,336; U.S. Pat. No. 4,376,115; German Offen. No. 2,907,406; Belgina No. 888,843. The use of sanguinarine with thiophosphoric acid for treating various human and animal neoplasms is shown in French Pat. Nos. 70-22029 and 2,152,972.
The benzo-c-phenanthridine alkaloids have been shown to have some antifungal and antiprotozoan properties. The antibacterial activity of benzo-c-phenanthridine alkaloids has been found to vary with the attached radicals, and various salts of the benzo-c-phenanthridine alkaloids have been found to have some activity against certain bacteria at various concentrations. Sanguinarine nitrate has been reported to have some weak bacteriostatic action on various types of bacteria.